Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

Salas-Zúñiga, Reynaldo; Rodríguez-Ruiz, Christian; Höpfl, Herbert; Morales-Rojas, Hugo; Sánchez-Guadarrama, Obdulia; Rodríguez-Cuamatzi, Patricia; Herrera-Ruiz, Dea

Pharmaceutics 2020, 12, x 10 of 18 physical mixture of NTZ and SUC (p > 0.05). However, for the formulations with 2.5 and 5.0% (w/w) of polymer, the AUC for the NTZ-SUC cocrystal increased by factors of 8.0 and 9.2, respectively, in comparison to the unformulated NTZ. Meanwhile, for NTZ and the physical mixture with SUC the AUC are practically constant in the polymer formulations examined herein. Selected samples of the solid residues recovered after the dissolution tests were analyzed by PXRD and SEM analysis. The PXRD data showed that the NTZ-SUC cocrystal is transformed into its parent drug in all of the formulations tested (Figure 8) , and it was also observed in the dissolution experiments under non-sink conditions. Peaks for SUC are not observed, indicating that the coformer was completely dissolved, which is in agreement with its good solubility in water (71 mg/mL at 25 °C). and solid residues after dissolution tests in USP 1 apparatus: (d) NTZ-SUC formulated with 1.0% w/w Methocel ® 60 HG, (e) NTZ-SUC formulated with 2.5% w/w Methocel ® 60 HG, (f) NTZ-SUC formulated with 5.0% w/w Methocel ® 60 HG, (g) NTZ formulated with 5.0% w/w Methocel ® 60 HG, and (h) physical mixture of NTZ and SUC formulated with 5.0% w/w Methocel ® 60 HG. Figure 9 presents SEM images of the cocrystal phase NTZ-SUC before and after the dissolution experiments in the presence of different amounts of Methocel ® 60 HG. Freshly prepared NTZ-SUC cocrystals exhibit a characteristic and homogeneous cylindrical morphology with a small particle size (Figure 9a ) in comparison with pure NTZ and the physical mixture with SUC ( Figure S5a,b) . The SEM images of the solid residues recovered after the dissolution tests of NTZ and the physical mixture formulated with Methocel ® 60 HG at 1.0 and 5.0% (w/w) show slight changes of the morphology in the presence of polymer ( Figure S5c-f) . A more pronounced effect occurs for the NTZ-SUC cocrystals with the morphology of the samples changing significantly with increasing amount of polymer (Figure 9b-d) .